Oskarsson A, Fowler B A
Exp Mol Pathol. 1985 Dec;43(3):397-408. doi: 10.1016/0014-4800(85)90076-0.
The effect of Pb pretreatment on the subcellular binding of a tracer dose of 203Pb was studied in kidneys of rats in which intranuclear and cytoplasmic inclusion bodies had been induced by a single ip injection of Pb acetate (50 mg Pb/kg) 6 days earlier. Results of subcellular fractionation studies in rats injected iv with 203Pb 24 hr prior to sacrifice demonstrated that 203Pb activity was about 1.5 times higher in kidney homogenates and mitochondrial fractions of control compared to Pb-pretreated rats. Cytosolic 203Pb activity in control rats was 5 times higher than that in Pb-pretreated rats. In contrast, Pb pretreatment increased the 203Pb binding capacity to the nuclear and inclusion body fractions by 7 and 20 times, respectively, compared with controls. Pb pretreatment decreased total mitochondrial 203Pb binding but resulted in a higher proportion of 203Pb bound to the inner membrane and matrix fractions relative to the controls. After in vitro incubation of control renal mitochondria with 203Pb the binding to inner and outer membranes and matrix fractions increased with increasing concentration of unlabeled lead added to the incubation. Deposits on the inner membrane of isolated mitochondria from Pb-pretreated rats were observed by isotonic ammonium molybdate negative staining and these mitochondria also showed decreased respiratory control ratios (RCRs). Succinate-mediated respiration rates and membrane binding of the fluorescent probe ethidium bromide were not affected by Pb pretreatment. These data indicate that lead influences its own subcellular distribution in the kidney following Pb pretreatment as shown by the increase of nuclear and inclusion body binding and increase of mitochondrial inner membrane and matrix binding of lead. The mitochondrial inner membrane shows a preferential affinity for lead following in vivo treatment which can be correlated with impairment of a specific inner membrane function (depressed RCRs). Lead exposure did not alter the activity of the mitochondrial membranes to undergo energy linked conformational changes.
研究了铅预处理对微量示踪剂量的²⁰³Pb在大鼠肾脏亚细胞结合的影响。这些大鼠在6天前经腹腔注射醋酸铅（50mg铅/千克）诱导形成了核内和胞质包涵体。在处死前24小时经静脉注射²⁰³Pb的大鼠中进行亚细胞分级分离研究的结果表明，与铅预处理的大鼠相比，对照大鼠肾脏匀浆和线粒体组分中的²⁰³Pb活性高约1.5倍。对照大鼠胞质中的²⁰³Pb活性比铅预处理大鼠高5倍。相反，与对照相比，铅预处理使²⁰³Pb与核及包涵体组分的结合能力分别提高了7倍和20倍。铅预处理降低了线粒体中²⁰³Pb的总结合量，但导致与内膜和基质组分结合的²⁰³Pb比例相对于对照更高。对照肾线粒体与²⁰³Pb进行体外孵育后，随着孵育体系中未标记铅浓度的增加，与内膜、外膜和基质组分的结合增加。通过等渗钼酸铵负染观察到铅预处理大鼠分离线粒体的内膜上有沉积物，这些线粒体的呼吸控制率（RCR）也降低。琥珀酸介导的呼吸速率和荧光探针溴化乙锭的膜结合不受铅预处理的影响。这些数据表明，铅预处理后，铅会影响其自身在肾脏中的亚细胞分布，表现为核和包涵体结合增加以及线粒体内膜和基质结合增加。体内处理后，线粒体内膜对铅表现出优先亲和力，这可能与特定内膜功能受损（RCR降低）有关。铅暴露并未改变线粒体膜发生能量相关构象变化的活性。
